553 research outputs found

    The long noncoding RNA RNCR2 directs mouse retinal cell specification

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    <p>Abstract</p> <p>Background</p> <p>Recent work has identified that many long mRNA-like noncoding RNAs (lncRNAs) are expressed in the developing nervous system. Despite their abundance, the function of these ncRNAs has remained largely unexplored. We have investigated the highly abundant lncRNA RNCR2 in regulation of mouse retinal cell differentiation.</p> <p>Results</p> <p>We find that the RNCR2 is selectively expressed in a subset of both mitotic progenitors and postmitotic retinal precursor cells. ShRNA-mediated knockdown of RNCR2 results in an increase of both amacrine cells and Müller glia, indicating a role for this lncRNA in regulating retinal cell fate specification. We further report that RNCR2 RNA, which is normally nuclear-retained, can be exported from the nucleus when fused to an IRES-GFP sequence. Overexpression of RNCR2-IRES-GFP phenocopies the effects of shRNA-mediated knockdown of RNCR2, implying that forced mislocalization of RNCR2 induces a dominant-negative phenotype. Finally, we use the IRES-GFP fusion approach to identify specific domains of RNCR2 that are required for repressing both amacrine and Müller glial differentiation.</p> <p>Conclusion</p> <p>These data demonstrate that the lncRNA RNCR2 plays a critical role in regulating mammalian retinal cell fate specification. Furthermore, we present a novel approach for generating dominant-negative constructs of lncRNAs, which may be generally useful in the functional analysis of this class of molecules.</p

    Design of an airborne launch vehicle and an air launched space booster

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77293/1/AIAA-1993-3955-297.pd

    Electron-ion recombination of Si IV forming Si III: Storage-ring measurement and multiconfiguration Dirac-Fock calculations

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    The electron-ion recombination rate coefficient for Si IV forming Si III was measured at the heavy-ion storage-ring TSR. The experimental electron-ion collision energy range of 0-186 eV encompassed the 2p(6) nl n'l' dielectronic recombination (DR) resonances associated with 3s to nl core excitations, 2s 2p(6) 3s nl n'l' resonances associated with 2s to nl (n=3,4) core excitations, and 2p(5) 3s nl n'l' resonances associated with 2p to nl (n=3,...,infinity) core excitations. The experimental DR results are compared with theoretical calculations using the multiconfiguration Dirac-Fock (MCDF) method for DR via the 3s to 3p n'l' and 3s to 3d n'l' (both n'=3,...,6) and 2p(5) 3s 3l n'l' (n'=3,4) capture channels. Finally, the experimental and theoretical plasma DR rate coefficients for Si IV forming Si III are derived and compared with previously available results.Comment: 13 pages, 9 figures, 3 tables. Accepted for publication in Physical Review

    A Throughfall Collection Method Using Mixed Bed Ion Exchange Resin Columns

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    Measurement of ionic deposition in throughfall is a widely used method for measuring deposition inputs to the forest floor. Many studies have been published, providing a large database of throughfall deposition inputs to forests. However, throughfall collection and analysis is labor intensive and expensive because of the large number of replicate collectors needed and because sample collection and chemical analyses are required on a stochastic precipitation event-based schedule. Therefore we developed and tested a throughfall collector system using a mixed bed ion exchange resin column. We anticipate that this method will typically require only one to three samplings per year. With this method, bulk deposition and bulk throughfall are collected by a funnel or snow tube and ions are retained as the solution percolates through the resin column. Ions retained by the resin are then extracted in the same column with 2N KCl and analyzed for nitrate and ammonium. Deposition values in throughfall from conventional throughfall solution collectors and colocated ion exchange samplers were not significantly different during consecutive 3- and 4-month exposure periods at a high (Camp Paivika; >35 kg N ha-1 year-1) and a low deposition (Barton Flats; 5–9 kg N ha-1 year-1) site in the San Bernardino Mountains in southern California. N deposition in throughfall under mature pine trees at Camp Paivika after 7 months of exposure was extremely high (87 and 92 kg ha-1 based on the two collector types) compared to Barton Flats (11 and 13 kg ha-1). A large proportion of the N deposited in throughfall at Camp Paivika occurred as fog drip, demonstrating the importance of fog deposition as an input source of N at this site. By comparison, bulk deposition rates in open areas were 5.1 and 5.4 kg ha-1 at Camp Paivika based on the two collector types, and 1.9 and 3.0 kg ha-1 at Barton Flats

    A surprising method for polarising antiprotons

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    We propose a method for polarising antiprotons in a storage ring by means of a polarised positron beam moving parallel to the antiprotons. If the relative velocity is adjusted to v/c0.002v/c \approx 0.002 the cross section for spin-flip is as large as about 210132 \cdot 10^{13} barn as shown by new QED-calculations of the triple spin-cross sections. Two possibilities for providing a positron source with sufficient flux density are presented. A polarised positron beam with a polarisation of 0.70 and a flux density of approximately 1.510101.5 \cdot 10^{10}/(mm2^2 s) appears to be feasible by means of a radioactive 11^{11}C dc-source. A more involved proposal is the production of polarised positrons by pair production with circularly polarised photons. It yields a polarisation of 0.76 and requires the injection into a small storage ring. Such polariser sources can be used at low (100 MeV) as well as at high (1 GeV) energy storage rings providing a time of about one hour for polarisation build-up of about 101010^{10} antiprotons to a polarisation of about 0.18. A comparison with other proposals show a gain in the figure-of-merit by a factor of about ten.Comment: 13 pages, 8 figures; v2: minor language and signification corrections v3: (14 pages, 12 figures) major error, nonapplicable polarisation transfer cross sections replaced by the mandatory spin-flip cross section

    A short isoform of STIM1 confers frequency-dependent synaptic enhancement

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    Store-operated Ca2+-entry (SOCE) regulates basal and receptor-triggered Ca2+ signaling with STIM proteins sensing the endoplasmic reticulum (ER) Ca2+ content and triggering Ca2+ entry by gating Orai channels. Although crucial for immune cells, STIM1’s role in neuronal Ca2+ homeostasis is controversial. Here, we characterize a splice variant, STIM1B, which shows exclusive neuronal expression and protein content surpassing conventional STIM1 in cerebellum and of significant abundance in other brain regions. STIM1B expression results in a truncated protein with slower kinetics of ER-plasma membrane (PM) cluster formation and ICRAC, as well as reduced inactivation. In primary wild-type neurons, STIM1B is targeted by its spliced-in domain B to presynaptic sites where it converts classic synaptic depression into Ca2+- and Orai-dependent short-term synaptic enhancement (STE) at high-frequency stimulation (HFS). In conjunction with altered STIM1 splicing in human Alzheimer disease, our findings highlight STIM1 splicing as an important regulator of neuronal calcium homeostasis and of synaptic plasticity

    Cell transformation assays for prediction of carcinogenic potential: State of the science and future research needs

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    Copyright @ 2011 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Cell transformation assays (CTAs) have long been proposed as in vitro methods for the identification of potential chemical carcinogens. Despite showing good correlation with rodent bioassay data, concerns over the subjective nature of using morphological criteria for identifying transformed cells and a lack of understanding of the mechanistic basis of the assays has limited their acceptance for regulatory purposes. However, recent drivers to find alternative carcinogenicity assessment methodologies, such as the Seventh Amendment to the EU Cosmetics Directive, have fuelled renewed interest in CTAs. Research is currently ongoing to improve the objectivity of the assays, reveal the underlying molecular changes leading to transformation and explore the use of novel cell types. The UK NC3Rs held an international workshop in November 2010 to review the current state of the art in this field and provide directions for future research. This paper outlines the key points highlighted at this meeting
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